Most patients with non-small cell lung cancer (NSCLC) present with unresectable disease and a large proportion have disease outside radiotherapy ports. Many drugs have been evaluated for NSCLC but they have been disappointing. Combination chemotherapy has not shown any convincing evidence of survival benefit independent of prognostic factors. Platinum, however, may play a role in combination chemotherapy. The current study thus utilizes cyclophosphamide, doxorubicin, and VP16 (active in oat cell carcinoma) + platinum. Sixty patients were entered on study; 33 received four drugs and 27 received three drugs. There are 4 complete responses (CR) and 5 partial responses (PR) for the four drug arm and four PR's in the three drug combination. It is too early to stratify for histologic subtypes or performance status. Toxicities include myelosuppression, mucositis and pharyngitis. Patients who fail primary chemotherapy receive phase II agents or secondline combinations. To date 20 patients have been studied with vindesine + platinum. There have been 0/12 responses for vindesine and 2/8 responses for the two drug combination. It is too early to develop stable response or survival information.